Growing cohorts of young non-injecting heroin users (NIHU) are making choices regarding drug injection that promise to shape the AIDS epidemic in Chicago and other U.S. cites for years to come. Despite the potential impact of NIHU on future AIDS trends, published research on this group in the U.S. is scarce and little is known about their transitions into injection. To help fill this void, we propose a five-year, longitudinal study of NIHU in Chicago that has three major aims: (1) measure the incidence of transitions by NIHU into drug injection and identify factors predicting this event; (2) measure the incidence and prevalence of HIV, hepatitis C, and hepatitis B infections among NIHU and identify factors associated with infection, and (3) explore the link between heroin use and risky sexual practices. The proposed study is grounded conceptually in social epidemiology, which models disease patterns as the product of interactions between an agent, host, and environment. The study will use a multi-method research design that combines a prospective epidemiologic survey, biologic testing, and qualitative interviewing. This design will enable causal analyses of the impact of independent variables on the outcomes of interest. The sample will consist of 1000 NIHU 16-30 years old recruited through respondent-driven sampling from areas across Chicago and its suburbs. Variable categories thought likely to predict major outcomes of interest are changing conditions in the properties and availability of heroin (agent/drug), individual characteristics (host/set), and the social settings within which drug use occurs (environment/setting). The goal of this study is to better understand current drug use patterns and HIV risk practices, particularly transitions to injection, among NIHU. We anticipate our findings being used to develop intervention strategies aimed at preventing drug injection and other HIV related behaviors among NIHU. To increase the scope and generalizability of findings, elements of the proposed study, including the survey questionnaire, have been designed for comparison with an ongoing NIDA-funded, prospective study of NIHU in New York City.